SHIELD-T1D: Shingrix and GLP-1 Agonist for Beta-Cell Preservation in Recent-Onset Type 1 Diabetes.

Sponsor
Ministry of Health, Saudi Arabia
Study ID
NCT07614412
Phase
PHASE2
Status
Not Yet Recruiting

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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 50 Years
Healthy Volunteers
Not accepted

Interventions

  • Recombinant Zoster Vaccine (Shingrix; RZV) — DRUG
    Intervention 1: Recombinant Zoster Vaccine (Shingrix; RZV) Drug/Biological: Recombinant zoster vaccine (lyophilized VZV glycoprotein E antigen 50 μg + AS01B adjuvant system \[MPL 50 μg + QS-21 50 μg in liposomal formulation\]). Dose: 0.5 mL intramuscular injection (reconstituted per manufacturer's instructions). Schedule: Two doses - Month 0 and Month 2 (8-week interval). Route: Intramuscular (deltoid, non-dominant arm preferred). Manufacturer: GlaxoSmithKline (GSK). FDA Status: Approved for herpes zoster prevention; use in T1D is investigational (IND required). Mechanism of Action: AS01B adjuvant promotes DC maturation, Th1 polarization, and regulatory T-cell induction via TLR4 (MPL) and saponin (QS-21) pathways
  • Semaglutide (Ozempic®) — DRUG
    Drug: Semaglutide - GLP-1 receptor agonist (acylated GLP-1 analogue with 94% sequence homology to native GLP-1). Dose Escalation: 0.25 mg SC once weekly (Weeks 1-4) → 0.5 mg SC once weekly (Weeks 5-24 months). Route: Subcutaneous injection (abdomen, thigh, or upper arm; rotate sites). Manufacturer: Novo Nordisk. FDA Status: Approved for T2D; investigational use in T1D (IND required). Mechanism of Action: GLP-1 receptor agonism enhances glucose-dependent insulin secretion, inhibits glucagon, promotes beta-cell survival and proliferation, reduces ER stress, and suppresses pro-inflammatory cytokine-mediated apoptosis (IL-1β, IFN-γ, TNF-α).
  • Placebo (saline injection) — DRUG
    Saline placebo administered as intramuscular injection (matching RZV volume 0.5 mL) at Months 0 and 2, and/or as subcutaneous injection (matching semaglutide volume) once weekly for 24 months. Used in control and single-active arms to maintain blinding.

Study Details

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by progressive destruction of pancreatic beta cells mediated by autoreactive T lymphocytes, resulting in absolute insulin deficiency. Preservation of residual beta-cell function at the time of diagnosis is a critical therapeutic window, as even marginal endogenous insulin secretion - reflected by detectable C-peptide levels - is associated with improved glycemic control, reduced hypoglycemia burden, and decreased long-term vascular complication rates. This study evaluates the hypothesis that combinatorial immunomodulation - using the AS01B adjuvant system within the Recombinant Zoster Vaccine (RZV; Shingrix, GSK) alongside metabolic and cytoprotective support via a GLP-1 receptor agonist (semaglutide) - can synergistically preserve residual beta-cell function in adults within 100 days of T1D diagnosis. The AS01B adjuvant system activates innate immune pathways that promote regulatory T-cell (Treg) expansion and shift the immunological milieu toward tolerance, while GLP-1 receptor agonism provides direct beta-cell cytoprotection, reduces glucotoxicity, and may suppress autoimmune cytokine signaling. SHIELD-T1D is a randomized, double-blind, placebo-controlled, parallel-group Phase II clinical trial enrolling 240 adults (18-50 years) diagnosed with T1D within 100 days, with confirmed residual beta-cell function (stimulated C-peptide ≥0.2 nmol/L). Participants are randomized 1:1:1:1 to one of four arms: (1) Shingrix alone, (2) Semaglutide alone, (3) Shingrix + Semaglutide combination, or (4) dual placebo. The primary endpoint is change in 2-hour stimulated C-peptide AUC during a Mixed Meal Tolerance Test (MMTT) from baseline to 12 months. This phase II randomized, double-blind, placebo-controlled multicenter trial will evaluate the efficacy and safety of the recombinant zoster vaccine (Shingrix) and a glucagon-like peptide-1 (GLP-1) receptor agonist, alone and in combination, for preservation of residual beta-cell function in adults with recent-onset type 1 diabetes. The working hypothesis is that combining AS01 adjuvant-mediated immunomodulation with the metabolic and cytoprotective actions of a GLP-1 receptor agonist will provide dual protection for pancreatic beta cells, slowing autoimmune destruction and improving functional insulin secretion compared with placebo.

Key Dates

First listed
May 29, 2026
Start date
Jan 1, 2027
Status verified
May 2026
Primary completion
Jan 31, 2028
Completion
Dec 31, 2028

Study Design

Enrollment
240 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Shingrix + Semaglutide Placebo
    RZV 0.5 mL IM at Months 0 and 2 + subcutaneous saline placebo once weekly for 24 months. Standard-of-care insulin therapy continues throughout
  • Active Comparator: Semaglutide + RZV Placebo
    Semaglutide 0.25 mg SC weekly for 4 weeks, then 0.5 mg SC weekly for 24 months + IM saline placebo at Months 0 and 2. Standard-of-care insulin throughout.
  • Experimental: Shingrix + Semaglutide (Combination
    RZV 0.5 mL IM at Months 0 and 2 + Semaglutide 0.25 mg SC weekly (escalating to 0.5 mg) for 24 months. Standard-of-care insulin throughout. PRIMARY EXPERIMENTAL ARM.
  • Placebo Comparator: Double placebo
    IM saline placebo at Months 0 and 2 + subcutaneous saline placebo once weekly for 24 months. Standard-of-care insulin throughout

Primary Outcome Measure

Change in 2-hour stimulated C-peptide Area Under the Curve (AUC) during a Mixed Meal Tolerance Test (MMTT) [ Time Frame: Baseline and 12 months ]

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